Corcuera Pindado M T, Lopez Bravo A, Martinez-Rodriguez R, Picazo Talavera A, Gomez Aguado F, Roldan Contreras M, Perez Alvarez M J, Fernandez Garcia A, Alonso Martin M J
Departamento de Anatomia Patologica, Instituto de Salud Carlos III, Universidad Complutense, Madrid.
Eur J Histochem. 1994;38(4):311-8.
Zidovudine (azidothymidine, AZT), a drug used in acquired immune deficiency syndrome (AIDS), blocks reverse transcriptase and therefore inhibits human immunodeficiency virus (HIV) replication. We carried out an ultrastructural and histoenzymatic study in rat cardiac muscle. Groups of animals (3 rats per group) were given drinking water with or without AZT (1 or 2 mg AZT/ml). After 30, 60 and 120 days, the hearts were studied by light and electron microscopy. Histochemical analysis of isocitrate, succinic, malic, NADH and NADPH dehydrogenase activities revealed no changes in AZT-treated rats compared with control rats. The ultrastructural study showed a disruption of cristae and an increased size of mitochondria in rats treated with AZT for 30- and 60-days. No alterations were observed in rats that received the 120-day treatment. A statistical analysis based on electron micrographs demonstrated a time-dependent ratio between intact and disrupted mitochondria. Rats that received AZT for 30 days showed a higher number of abnormal mitochondria than rats that received the 60 day treatment. No differences with respect to rat controls were observed in the rats that received AZT for 120 days. We conclude that AZT-induced ultrastructural alterations in cardiac muscle did not modify the histochemical activity of several mitochondrial enzymes.
齐多夫定（叠氮胸苷，AZT）是一种用于治疗获得性免疫缺陷综合征（艾滋病）的药物，它能阻断逆转录酶，从而抑制人类免疫缺陷病毒（HIV）的复制。我们对大鼠心肌进行了超微结构和组织酶学研究。将动物分组（每组3只大鼠），分别给予含或不含AZT（1或2毫克AZT/毫升）的饮用水。30、60和120天后，通过光学显微镜和电子显微镜对心脏进行研究。对异柠檬酸、琥珀酸、苹果酸、NADH和NADPH脱氢酶活性的组织化学分析显示，与对照大鼠相比，接受AZT治疗的大鼠没有变化。超微结构研究表明，接受AZT治疗30天和60天的大鼠线粒体嵴遭到破坏，线粒体体积增大。接受120天治疗的大鼠未观察到改变。基于电子显微镜照片的统计分析表明，完整线粒体与受损线粒体之间存在时间依赖性比例关系。接受AZT治疗30天的大鼠比接受60天治疗的大鼠有更多异常线粒体。接受AZT治疗120天的大鼠与大鼠对照组相比未观察到差异。我们得出结论，AZT诱导的心肌超微结构改变并未改变几种线粒体酶的组织化学活性。
